TOF mass spectrometry is an analytical technique for measuring the mass/charge ratio of ions by accelerating ions and measuring their time of flight to an ion detector.
In a simple form, a TOF mass spectrometer includes an ion source for generating a pulse (or burst) of ions of sample material and an ion detector for detecting ions that have travelled from the ion source to the ion detector. The ions generated by the ion source preferably have, e.g. because they have been accelerated to, a predetermined kinetic energy and so have different speeds according to their mass/charge ratio. Accordingly, as ions travel between the ion source and the ion detector, ions of different mass/charge ratios are separated by their different speeds and so are detected by the ion detector at different times, which allows their respective times of flight to be measured based on an output of the ion detector. In this way, mass spectrum data representative of the mass/charge ratio of ions of sample material can be acquired based on an output of the ion detector.
Matrix-assisted laser desorption/ionization, often referred to as “MALDI”, is an ionisation technique in which, generally, a laser is used to fire light at a (usually crystalised) mixture of sample material and light absorbing matrix so as to ionise the sample material. The sample materials used with MALDI typically include molecules such as biomolecules (e.g. proteins), large organic molecules and/or polymers. The light absorbing matrix is generally used to protect such molecules from being damaged or destroyed by light from the laser. The resulting ions, which typically have masses of several thousand Daltons, are then accelerated to high kinetic energies, typically around 20 keV. Generally, an ion source configured to generate ions by MALDI is referred to as a “MALDI ion source”. A MALDI ion source typically includes a laser for ionising sample material by firing light at a mixture of the sample material and light absorbing matrix.
MALDI is usually combined with time of flight mass spectrometry to provide “MALDI TOF” mass spectrometry in which, generally, a pulse of ions is generated by MALDI and the time of flight of the ions is then measured over distances typically of around 1-2 meters so that the mass/charge ratio of the ions can be determined.
Measuring the time of flight of ions in modern TOF mass spectrometers, e.g. MALDI TOF mass spectrometers, typically requires a diverse range of high speed digital and analogue electronics. For example, high speed timing electronics may be used in order to accurately synchronise various high-voltage electrical pulses with the firing of a laser and the acquisition of an ion signal. Also, kV/μs slew-rate high voltage electrical pulses may be used to accelerate, gate and steer ionised molecules generated by the laser. Finally, high speed multi-bit analogue to digital converters may be used to record the output from an ion detector so that the time of flight of the ions, and therefore the mass/charge ratio of the ions, can be determined. Such high speed digital and analogue electronics are typically run for each acquisition cycle of the TOF mass spectrometer.
Until recently, TOF mass spectrometers, e.g. MALDI TOF mass spectrometers, have used gas lasers having a repetition rate (rate at which it can fire pulses of light) of up to a few tens of Hz. More recent TOF mass spectrometers have used solid-state lasers capable of much higher repetition rates, e.g. 1 kHz or more.
The present inventors have found that high repetition rates of solid state lasers, combined with increasing clock speeds of digital electronics, has introduced new problems in the design of TOF mass spectrometers, particularly MALDI TOF mass spectrometers. These design problems include:                how to generate control data for controlling one or more components of a mass spectrometer with multiple high-precision delays (e.g. with microsecond durations and sub-nanosecond resolution);        how to stabilise power supplies to the electronics without radiating a lot of narrow-band electrical noise, especially for high-voltage pulses; and        how to reduce the manifestation of noise in mass spectrum data produced by such MALDI TOF mass spectrometers.        
A mass spectrometer preferably includes timing electronics for producing one or more control signals for controlling the operation of one or more components of the mass spectrometer such that the control signals are synchronised to a trigger event indicated by a trigger signal and/or for adjusting data produced by an analogue to digital converter of the mass spectrometer such that the adjusted data is synchronised to a trigger event indicated by a trigger signal. The trigger event may, for example, be the firing of a laser for ionising sample material.
Previously, the present inventors have used high speed positive-emitter-coupled logic (PECL) circuitry in the timing electronics of mass spectrometers. In such timing electronics, many separate PECL integrated circuits were used together to produce control signals synchronised to a trigger event indicated by trigger signal. These PECL integrated circuits were typically controlled by an FPGA integrated circuit, which could also be used to control other functionality of a transient recorder of the mass spectrometer.
Presently available PECL circuitry is capable of running at clock speeds of around 500 MHz. Consequently, the time resolution of such PECL circuitry is around 2 ns. However, there are several disadvantages associated with using PECL circuitry for the timing electronics of a mass spectrometer. Firstly, modern mass spectrometers may require digitisation speeds of many GHz, with timing electronics having a time resolution of less than a nanosecond. Such speeds and time resolution are difficult, if not impossible, to achieve with presently available PECL circuitry. Secondly, the complexity of the PECL circuitry involves many individual components, and so is difficult to implement for many separate PECL integrated circuits. This can add to the cost of the timing electronics of a mass spectrometer and mean that a large amount of printed circuit board real estate is required. Thirdly, as the PECL circuitry can be large and complex, the PECL circuitry may be unreliable, especially when manufacturing circuit boards. Finally, PECL circuitry cam be prone to disturbance by electrical noise and can also add to the EMC noise radiated by the circuit board.